Phase II study of the histone deacetylase inhibitor belinostat (PXD101) for the treatment of myelodysplastic syndrome (MDS).
Phase II study of the histone deacetylase inhibitor belinostat (PXD101) for the treatment of myelodysplastic syndrome (MDS).
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DOI：
10.1007/s00277-011-1240-1
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发表时间：
2012-01
影响因子：
3.5
通讯作者：
DiPersio, John
中科院分区：
文献类型：
--
作者：
Cashen, Amanda;Juckett, Mark;Jumonville, Alcee;Litzow, Mark;Flynn, P. J.;Eckardt, John;LaPlant, Betsy;Laumann, Kristina;Erlichman, Charles;DiPersio, John
组蛋白去乙酰化酶（HDAC）的抑制可以诱导癌细胞分化、生长停滞和凋亡。这项II期多中心研究旨在评估贝利司他（一种I类和II类HDAC酶的强效抑制剂）治疗骨髓增生异常综合征（MDS）的疗效。既往接受过≤2次治疗的MDS成人患者在21天周期的第1-5天接受贝利司他1，000 mg/m2 IV治疗。主要终点是治疗前12周内确认的缓解比例。缓解的患者可以接受额外的周期，直到疾病进展或不可接受的毒性。入组了21例患者，均为可评价患者。患者的中位诊断时间为13.4个月，14例患者（67%）的骨髓原始细胞低于5%。17例患者（81%）依赖输血。既往治疗包括氮杂胞苷（n=7）和化疗（n=8）。患者接受了中位4个周期（范围1-8）的贝利司他治疗。有一个确认的反应-血液学改善的嗜中性粒细胞-总反应率为5%（95%CI，0.2-23）。中位总生存期为17.9个月。认为至少可能与贝利司他相关的3-4级毒性为：中性粒细胞减少症（n=10）、血小板减少症（n=9）、贫血（n=5）、疲乏（n=2）、发热性中性粒细胞减少症（n=1）、头痛（n=1）和QTc延长（n=1）。由于研究在入组的第一阶段符合停止规则，因此关闭进一步入组。
The inhibition of histone deacetylase (HDAC) can induce differentiation, growth arrest, and apoptosis in cancer cells. This phase II multicenter study was undertaken to estimate the efficacy of belinostat, a potent inhibitor of both class I and class II HDAC enzymes, for the treatment of myelodysplastic syndrome (MDS). Adults with MDS and ≤2 prior therapies were treated with belinostat 1,000 mg/m2 IV on days 1–5 of a 21-day cycle. The primary endpoint was a proportion of confirmed responses during the first 12 weeks of treatment. Responding patients could receive additional cycles until disease progression or unacceptable toxicity. Twenty-one patients were enrolled, and all were evaluable. Patients were a median 13.4 months from diagnosis, and 14 patients (67%) had less than 5% bone marrow blasts. Seventeen patients (81%) were transfusion dependent. Prior therapy included azacytidine (n=7) and chemotherapy (n=8). The patients were treated with a median of four cycles (range, 1–8) of belinostat. There was one confirmed response—hematologic improvement in neutrophils—for an overall response rate of 5% (95% CI, 0.2–23). Median overall survival was 17.9 months. Grades 3–4 toxicities considered at least to be possibly related to belinostat were: neutropenia (n=10), thrombocytopenia (n=9), anemia (n=5), fatigue (n=2), febrile neutropenia (n=1), headache (n=1), and QTc prolongation (n=1). Because the study met the stopping rule in the first stage of enrollment, it was closed to further accrual.
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影响因子：
20.3
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